There is evidence supporting the idea that many viruses, and HTLV-1 in particular, may require cell-cell adhesion for transmission. Accumulation and transfer of virion components at sites of cell-cell contact have been visualized by light and electron microscopy. Whether these images represent true infection events is not known. Although it is believed that infection of target cells is more efficient when cocultured with virus-producing cells than when infected with cell-free virus, there has not been a good experimental method to show that this is due to cell-to-cell transmission. To address this important issue, we have constructed HTLV-1 and HIV-1 vectors and developed cell culture methods that will make it possible to analyze cell-to-cell infection. Combined with biochemical and microscopic image analysis, the new methods will help to define how polarized virus assembly, release, transfer, and entry are coordinated with adhesion-induced changes in cell morphology. In addition the HIV-1 and HTLV-1 vectors that we have developed are central to new, high throughput infectivity assays for screening antiviral agents. [Corresponds to Derse Project 2 in the April 2007 site visit report of the HIV Drug Resistance Program]